T cell recruiters are antibodies designed to redirect the immune system’s T cells to recognize and kill cancer cells. They are designed to bind to a target antigen expressed on a cancer cell and trigger a molecule on T cells. These therapeutic molecules then engage T cells that are present in tumors but are unable to recognize cancer cells, redirecting their activity to the tumor.

Despite being primarily investigated to treat cancer, T-cell engagers may also have the potential to treat autoimmune diseases, particularly those driven by B cells, such as systemic lupus erythematosus and lupus nephritis, as these therapies can lead to profound depletion of B cells in the bloodstream. and tissues.

In this article, we take a look at five T-cell recruitment companies that are leading the way in this emerging field.

Adaptin Bio

With out of stealth in early September 2024, Adaptin Bio is developing precision cancer therapies with enhanced delivery to the brain and other tissues. At the same time as it came out of hiding, the company announced that it had received US Food and Drug Administration (FDA) approval for its Investigational New Drug (IND) application for its lead program, APTN-101, in glioblastoma – the most common and most aggressive type of primary brain tumor.

APTN-101 is a Brain Bispecific T Cell Engager (BRiTE) created with the patented Adaptin platform technology, which uses a combination of specifically engineered T cells with bispecific antibodies to enhance the delivery of bispecific antibodies to tissues of interest, including the brain. APTN-101 works by simultaneously targeting the EGFRvIII mutation, a variant commonly found in gliomas, and the CD3 receptor on T cells, in turn ensuring that the treatment is localized and effective, as well as harnessing the body’s own defense mechanisms body by activating T. cells and directing them to attack tumor cells.

According to the company, in preclinical studies, APTN-101 has demonstrated impressive efficacy in eliminating malignant glioma tumors in various aggressive orthotopic models. The FDA’s recent approval will now allow the initiation of a first-in-human phase 1 study to evaluate the drug candidate in patients who have been diagnosed with WHO grade 4 malignant glioma (based on the World Health Organization’s own (WHO) grading system) . Adaptin is also in the process of evaluating additional BRiTE targets.

Honest therapy

Another company that came out in September is Candid Therapeutics, release with one of the largest private investments of the month after it managed to raise capital of 370 million dollars. The company is developing T cell-engaging antibodies that can deplete specific B lymphocyte cell populations for the treatment of autoimmune diseases and aims to be the first to bring these novel therapies to market.

In an unusual move, the launch of the T-cell recruiting company also involved the acquisition of two biotech companies, Vignette Bio and TRC 2004, and their core assets, CND106 and CND261, respectively. CND106 targets B-cell maturation antigen, while CND261 binds to CD20. Both then bind to CD3 on the surface of T cells.

Both candidates have completed phase 1 dose escalation studies with combined data from over 130 oncology patients. Candid is now focused on filing IND applications for them so the company can study them in autoimmune diseases. Ken Song, Chairman, President and Chief Executive Officer (CEO) of Candid, said Fierce Biotech that they hope to have clinical data on drug safety by at least 2025.

Therapeutic clasp

Therapeutic clasp launch in March 2024 with $150 million to develop precision T-cell recruits that are matched to patients with specific immune systems and tumor signatures to tackle hard-to-treat tumors.

The T-cell engagement company targets fragments of mutant proteins, or peptides, that are displayed by specialized human leukocyte antigen (HLA) molecules on the surfaces of cancer cells. This approach opens up the possibility of targeting the vast majority of cancer-driving proteins that are expressed exclusively inside the cell and are therefore invisible to traditional antibody-like drugs.

Clasp targets these protein fragments with pHLAre molecules, Clasp’s precision T cell recruits, which are designed to draw T cells into close contact with tumor cells. Clasp says the resulting immune synapse is very similar to a natural HLA molecule-T cell receptor interface, triggering T cells to destroy tumor cells while sparing non-malignant cells.

At the time of launch, the company said its funding was large enough to simply work on promoting its programs, but would not disclose what its current main asset is.

Janux Therapeutics

Janux Therapeutics aims to overcome the safety and efficacy limitations of traditional T-cell agents, which the company says have shown limitations in treating solid tumors, such as overactivation of the immune system leading to cytokine release syndrome (CRS), on target, off-target effects and poor pharmacokinetics leading to a short half-life. Therefore, Janux is using its platform masking technology to design new drug candidates, called tumor-activated T-cell recruiters (TRACTrs) and tumor-activated immunomodulators (TRACIrs), which are purposefully designed to enhance specific activation tumors with cross-pharmacokinetics to provide drugs with improved safety. , dosage and efficacy.

The company’s lead asset is a T-cell recruiter called JANX007, which is being tested in patients with advanced or metastatic prostate cancer and targets prostate-specific membrane antigen (PSMA) and CD3. PSMA a protein expressed in prostate cancer tumors and tumor vasculature and is in the clinic for the treatment of metastatic castration-resistant prostate cancer.

In February 2024, Janux announced encouraging data for JANX007 from its ongoing phase 1a study. Of the 18 patients who received an initial dose of 0.1 mg, 14 (78%) achieved a decrease in prostate-specific antigen (PSA) of at least 30%, with 10 of these patients (56%) achieving a decrease of 50%. At the time, according to Fierce Biotechanalysts at William Blair also said this reading raised their JANX007 success estimate from 40% to 60%.

Therapeutic lava

Lava Therapeutics NV is focused on advancing its proprietary Gammabody platform to develop a portfolio of bispecific gamma-delta T cell recruits for the potential treatment of solid tumors and hematologic malignancies.

These drugs activate a subset of unique and relatively abundant effector gamma delta T cells called Vγ9Vδ2 (Vgamma9 Vdelta2) T cells, which are the largest T cell subpopulation in healthy adults and occur naturally in the human immune system. They essentially have a tumor recognition mechanism that allows them to specifically recognize and kill cells under stress, such as cancer cells, while leaving healthy cells unharmed. The company’s approach is designed to take full advantage of this natural tumor recognition to direct Vγ9Vδ2 T cells to the tumor, selectively kill cancer cells and trigger an immune response cascade.

Lava’s lead program is called LAVA-1207 and is being developed for patients with metastatic castration-resistant prostate cancer. It is currently being tested in a phase 1/2a study. T-cell hiring company also recently signed a partnership agreement with Merck to evaluate LAVA-1207 with Keytruda. Accordingly, Lava plans to expand its Phase 1/2a study to include a combination arm with Keytruda.

The T cell recruitment field is set to take off

Some big names in the biotech and pharmaceutical industries have begun developing or investing in T-cell workers, including Regeneron, which recently received green light from the European Commission (EC) for its committed T-cell treatment for two types of blood cancer and Amgen, which present positive data last year for its T-cell involved tarlatamab in patients with small cell lung cancer. Additionally, as can be seen from this list, several biotech companies have recently launched specifically to develop these types of drugs.

This surge in interest in T-cell workers suggests that the field is set to break out, and it probably won’t be long before we see more drugs of this type hit the market.